We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00185731
First Posted: September 16, 2005
Last Update Posted: December 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
The Leukemia and Lymphoma Society
Damon Runyon Cancer Research Foundation
Burroughs Wellcome
Information provided by (Responsible Party):
Dean Felsher, Stanford University
  Purpose
This is an approach which can inflict significant toxicity. An alternative is to block expression of oncogenes which are over-expressed only in cancer cells, a therapeutic approach which could reduce toxicity to the host while maximizing destruction of the oncogene-dependent malignant cells.

Condition Intervention Phase
Leukemia Lymphoma, Non-Hodgkin Drug: Atorvastatin Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Atorvastatin in Patients With Low Grade or Refractory Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Dean Felsher, Stanford University:

Primary Outcome Measures:
  • Tumor Apoptosis [ Time Frame: 1 year ]
    Expressed as the number of participants whose tumor cells showed an increase in apoptosis during atorvastatin treatment


Secondary Outcome Measures:
  • Correlation of Tumor Apoptosis to Clinical Response [ Time Frame: 1 year ]
    The validity of tumor apoptosis as a biologic endpoint was assessed by correlation to clinical response. A correlation substantially less than 1 is interpreted as a poor correlation, while a correlation near +1 or -1 is interpreted as a strong correlation.

  • Atorvastatin Toxicity [ Time Frame: 1 year ]
    Assessed as the number of study participants with atorvastatin-related serious adverse events (SAEs).


Enrollment: 25
Study Start Date: April 2005
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 80 mg Atorvastatin
Atorvastatin, 80 mg tablet, will be taken orally by the patient daily, beginning on study day 1.
Drug: Atorvastatin
80 mg orally once daily
Other Name: Lipitor

Detailed Description:
Atorvastatin has been shown to decrease levels of active oncogenes in preclinical studies with murine and human lymphoma cell lines, and administration of statins leads to shrinkage of lymphoma in murine models. Therefore, it may be possible for atorvastatin to decrease levels of active oncogenes in human lymphomas. Further, upon decrease in levels of active oncogenes, human lymphomas may regress. Atorvastatin is a commonly prescribed drug for hypercholesterolemia: targeting the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme may also be a way to decrease activation of oncogenes in human lymphoma, with minimal toxicity. For human low grade non-Hodgkin lymphoma, no curative treatment is available; therefore new, non-toxic and targeted therapies are sought for this disease.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • > 18 years old
  • Disease criteria: Confirmed by Stanford Pathology to be one of the following Non-Hodgkin's Lymphoma (NHL) subtypes:

    • Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL)
    • Extranodal marginal zone B-cell lymphoma
    • Nodal marginal zone B-cell lymphoma
    • Splenic marginal zone B-cell lymphoma
  • Treatment criteria

    • Untreated: watchful waiting currently appropriate (includes CLL stage 0) o OR
    • Prior treatment: watchful waiting currently appropriate o OR
    • Refractory disease
  • Staging within 4 weeks prior to enrollment (SLL, marginal zone lymphoma)

    • CT chest (date)
    • CT abdomen (date)
    • CT pelvis (date) OR
  • Staging within 4 weeks prior to enrollment (CLL: CT not required)

    • Total white blood cell count (WBC) (Value) (date)
    • Absolute lymphoma cell count (ALC) (Value) (date)
    • Measurable disease (Site) (Size) OR
    • CLL (only): elevated absolute lymphoma cell count
  • Disease amenable to biopsy (must check at least one):

    • Circulating tumor cells
    • Positive bone marrow
    • Palpable involved site (such as lymph node) measuring > 1.5 cm
  • Eastern Cooperative Oncology Group performance status <2 (Karnofsky >60)
  • Life expectancy of greater than 3 months
  • Patients must have adequate organ and marrow function

    • Absolute neutrophil count > 1,000/uL
    • Platelets > 30,000/uL
    • Total bilirubin within normal institutional limits
    • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ratio < 2.5 x institutional upper limit of normal
    • Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must have negative BetaHCG at enrollment

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Not recovered from adverse events due to agents administered more than four weeks earlier
  • Has stable low grade lymphoma has had rituximab within 3 months Patient with relapsed or refractory disease has had rituximab within 1 month
  • Not recovered from adverse events due to surgery performed 4 weeks earlier
  • Receiving any other investigational agent. Known brain metastases
  • Taken any statin within the past 6 months prior to enrollment in the trial
  • Currently abuses alcohol
  • Currently takes cyclosporin or gemfibrozil Patient has a prior history of rhabdomyolysis
  • Has uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant: Patients are not excluded if they are breastfeeding at the time of enrollment, but breastfeeding should be discontinued if the mother is treated with atorvastatin.
  • HIV-positive patients receiving combination anti-retroviral therapy
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00185731


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Dean Felsher
The Leukemia and Lymphoma Society
Damon Runyon Cancer Research Foundation
Burroughs Wellcome
Investigators
Principal Investigator: Dean Felsher Stanford University
  More Information

Responsible Party: Dean Felsher, Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00185731     History of Changes
Other Study ID Numbers: IRB-13683
4328-07 ( Other Identifier: Damon Runyon Cancer Research Foundation )
95140 ( Other Identifier: Stanford University Alternate IRB Approval Number )
LYMNHL0020 ( Other Identifier: OnCore )
First Submitted: September 12, 2005
First Posted: September 16, 2005
Results First Submitted: January 24, 2017
Results First Posted: December 1, 2017
Last Update Posted: December 1, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors